Gene discovery could lead to birth control pill for men

When it comes to birth control, numerous options are available to women to help them regulate their menstrual cycle and prevent ovulation. But what if a birth control pill for men were available?

That prospect may soon become a reality now that researchers at the University of Edinburgh have recently discovered a gene that is essential for the development of sperm. Their study, published in the journal PLos Genetics, highlights the gene Katnal1, which causes temporary infertility in male mice when blocked.

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In order to identify Katnal1 as a key element in sperm production, the researchers treated a group of mice with a chemical called ENU, which triggers mutations in the DNA. Afterward, they bred the mice to see if any of them became infertile. After establishing a group of impotent mice, they backtracked through genetic mapping to identify which gene had been disrupted by the ENU – leading them to Katnal1.

“Importantly the random nature of ENU, which causes changes in DNA at random, means we can identify important genes that otherwise we would have had no reason to suspect play a role in male fertility,” said Dr. Lee Smith, a reader in the department of genetic endocrinology at the University of Edinburgh as well as the study’s lead author. “For example, before this study, no one had any idea Katnal1 was even active in the testis, and as such, Katnal1 would probably not have been identified in any other way.”

Lee and his team further identified that Katnal1 was used to regulate a structure known as microtubules – parts of sperms that needed for support and the acquisition of nutrients. Breaking down these microtubules inhibits sperms’ ability to move throughout the testes during their maturation.

The gene’s discovery not only paves the way for a male contraceptive pill, but could also aid in better understanding cases of male infertility.

“As we move towards personalized medicine, comparing DNA sequences of infertile men against gene data provided from studies such as this will help clinicians identify the causes underlying unexplained male infertility,” Smith said. “If a genetic fault can be traced to a problem within the supporting cells of the testes rather than the sperm cells then it could be possible to use a gene-therapy approach to replace the faulty copy of the gene and restore fertility.”

However, a potential male contraceptive pill would not utilize gene-therapy, but instead would involve identifying a protein that is used to regulate Katnal1. According to Lee, if they are able to come up with a way to specifically target the gene’s function in the testes, then they could potentially create a non-hormonal contraceptive.

Also, a male pill would not only need to be effective in stopping sperm production but also be just as effective in having it start back up again. According to Smith, blocking Katnal1 would render a man sterile for the rest of his life.

“The important thing is that the effects of such a drug would be reversible,” Smith said in a press release,” because Katnal1 only affects sperm cells in the later stages of development, so it would not hinder the early stages of sperm production and the overall ability to produce sperm.”

Currently, there are not many options in the way of male pharmaceutical contraception. Recent options have included testosterone injections or testosterone plus progestin injections, which are used to trick the brain into thinking the testes have produced enough testosterone, so sperm production shuts down.

However, these options rely on hormones, while the potential drug to come from Lee and his team’s research would be hormone-free and could bypass the side-effects that come with increased testosterone levels – such as mood swings and acne.

Lee said that his team has much more research to do before this drug becomes available, but he said we could see its development within the next decade.

“We are at the beginning, but have taken a great step forward in identifying a new pathway that controls male fertility.”